This invention relates to detection and treatment systems for cancer and pre-cancer, and more specifically to a detection and treatment system that first detects cancerous and pre-cancerous tissue in situ, and then dynamically and automatically shapes and re-shapes its photodynamic therapy (PDT) treatment beam during the course of treatment to maximize the effect of the treatment beam while simultaneously minimizing the illumination of surrounding normal tissue.
Analyzing living cells using fluorescence of a dye, which is produced in an interaction between tissue and an injected chemical, is a well-understood method in the field of medical science. In this method of analysis, a chemical is introduced into living tissue, where the chemical is preferentially absorbed into cancerous or pre-cancerous cells. The chemical interacts with the living tissue to produce a dye. The dye is highly fluorescent, meaning that it absorbs a particular wavelength of light, and subsequently emits a longer wavelength of light. For example, a dye might absorb 340 nm light very well, and as a result of absorbing such light, will immediately emit large quantities of light in a band centered at 530 nm. Thus, many methods exist that involve introducing a drug into living tissue (either intravenously or topically), waiting for the drug to be interact with the tissue and produce a dye and to be preferentially absorbed by cancerous and pre-cancerous cells, and then illuminating an area of the tissue with 340 nm (ultraviolet) light, while simultaneously receiving light from the area with a detector that is sensitive only to 530 nm light (using a filter, for example, that allows only 530 nm light to pass through to the detector).
Another method for analyzing living cells involves looking at a series of narrow-wavelength-bands of reflected light from the tissue. In this process, broad-wavelength light (for example, white light spanning the range from 400 nm to 700 nm) is used to illuminate the sample. A high-resolution multispectral imager is then used to image the tissue at several different wavelength bands. With this method, it is possible to find locations where larger-than-normal densities of capillary blood vessels occur. The presence of larger-than-normal densities of capillary blood vessels (along with their shape, in some cases) may indicate the presence of cancerous and/or pre-cancerous cells.
Analyzing living cells using autofluorescence spectroscopy is also well understood in the field of medical science. In the process of autofluorescence no drug is introduced to the living tissue. Light of a particular wavelength is simply introduced to the living tissue, and through the process of autofluorescence, light of a longer wavelength is immediately emitted from the same tissue. Compared to the process of fluorescence of a dye, which is produced in an interaction of tissue with an injected drug (described above), the process of autofluorescence produces a great deal less emitted light. In addition, all living cells will emit light from naturally occurring flurophores within the cells.
Thus, the detection of emitted light, and especially the discrimination between light emitted from normal cells and that emitted from cancerous or pre-cancerous cells, becomes a difficult, two-part problem to solve. First, the fluorescence light must be efficiently detected and then the detected light must be processed with complex computer algorithms to discriminate between normal and cancerous/pre-cancerous cells. There are solutions to the problem in the prior art, most of these using spectroscopy or multispectral imaging. For example, U.S. Pat. No. 6,208,749, which is hereby incorporated by reference in its entirety, utilizes a filter wheel to provide images in at least three spectral bands, analyzes and characterizes each image, where the characteristics are useful in discriminating between normal and cancerous/pre-cancerous cells. The method presented in U.S. Pat. No. 6,208,749 does not obtain images simultaneously and does not provide a method for treatment of pre-cancer or cancerous cells. In U.S. Pat. Nos. 5,115,137 and 4,786,813, both of which are hereby incorporated by reference in their entirety, systems are described that utilize filters to segment the image into four images at separate spectral bands. Since the image is divided by filtering and detection, only a portion of the image is observed in each spectral band. Again, these methods do not provide a means of treatment for pre-cancer or cancerous cells.
In U.S. Pat. No. 6,135,965, Spectroscopic Detection of Cervical Precancer Using Radial Basis Function Networks, also hereby incorporated by reference in its entirety, the fluorescence spectra from a fiber optic fluorimeter at three excitation wavelengths are used to train a neural network for the detection of cervical pre-cancer. The neural network can then be used for detection of cervical pre-cancer. The method of U.S. Pat. No. 6,135,965 is non-imaging, is not coaxial and does not provide a means for treatment of pre-cancer or cancerous cells. In U.S. Pat. No. 6,256,530, also hereby incorporated by reference herein in its entirety, an intensity is measured in a wavelength range and the process repeated to compare intensities of two images at a given wavelength range. This difference is used to differentiate the response of cancerous cells from that of healthy cells. The method of U.S. Pat. No. 6,256,530 is non-imaging and provides a means only for detection, not for treatment of pre-cancer or cancerous cells. In U.S. Pat. No. 5,623,932, also hereby incorporated by reference herein in its entirety, the peak intensities and selected slope measurements of fluorescence spectra are used to differentiate the response of cancerous cells from that of healthy cells. The method in U.S. Pat. No. 5,623,932 for detection is non-imaging and further does not provide a means for treatment of pre-cancer or cancerous cells.
Photodynamic therapy (PDT) is a well-understood method for the treatment of cancerous and pre-cancerous conditions. In this method, a special chemical is introduced to the living tissue. This special chemical is a photo-activated drug that kills surrounding cells when it is activated with a certain wavelength of light. This special chemical is absorbed more by cancerous and pre-cancerous cells than by normal cells. However, normal cells do absorb some of the drug. Prior art descriptions of photo-dynamic therapy involve first injecting the patient with the special drug or applying the agent topically, and then bathing a large, non-descript area of the tissue with activating light. There are several implementations of treatment systems that have introduced elements to restrict or define the illumination area. In U.S. Pat. No. 5,514,127, hereby incorporated by reference in its entirety, a spatial light modulator (SLM) is used to irradiate a selected treatment area. U.S. Pat. No. 5,514,127 requires the use of an endoscope and additionally does not provide treatment simultaneously with detection. In U.S. Pat. No. 6,186,628, also hereby incorporated by reference in its entirety, an acousto-optic modulator (AOM) is used to scan the laser beam in order to customize its shape. The method in U.S. Pat. No. 6,186,628 requires scanning of the treatment beam.
In all of the above systems, the detection and treatment systems are separate and do not interact. Patient comfort, cost containment and health outcomes will be improved by a system in which detection and treatment interact.
It is therefore an object of this invention to detect and locate cancerous and/or pre-cancerous cells in living tissue using a multispectral imager and a comparison of the different-wavelength images and to adaptively and dynamically shape a PDT treatment beam using the images obtained with the multispectral fluorescence imager.